Method and apparatus for treatment of tissue

ABSTRACT

A method and apparatus is disclosed for determining the success of a proposed HIFU Treatment, of an ongoing HIFU Treatment, and/or of a completed HIFU Treatment. An energy density of a given HIFU Treatment may be used as a comparison factor between the given HIFU Treatment and other HIFU Treatments and as a predictor of the success of the given HIFU Treatment. One exemplary energy density is the amount of energy deposited in the treatment region divided by the volume of the treatment region. Another exemplary energy density is the amount of energy deposited in the treatment region divided by the pre-treatment mass of the treatment region. A method and apparatus is disclosed to detect the presence of focal hyperechoic features and non-focal hyperechoic features. A method and apparatus is disclosed to detect the presence of an acoustic obstruction.

FIELD OF THE INVENTION

The present invention relates to an apparatus and related method for thetreatment of tissue, and in particular, for the non-invasive treatmentof diseased tissue.

BACKGROUND AND SUMMARY OF THE INVENTION

Several techniques have been used in the past for the treatment oftissue including diseased tissue, such as cancer, to remove, destroy, orotherwise minimize the growth of the diseased tissue. For example,traditional methods of treating diseased prostate tissue include highintensity focused ultrasound (“HIFU”), radiation, surgery,Brachytherapy, cryoablation, hormonal therapy, and chemotherapy.Described herein are improved apparatus and method for treating tissuewith high intensity focused ultrasound.

Although the techniques, methods, and apparatus discussed herein haveapplicability to the treatment of tissue in general, this discussionwill focus primarily on the treatment of prostate tissue includingBenign Prostatic Hyperplasia (BPH) and prostatic cancer. However, thedisclosed apparatus and methods will find applications in localizationand treatment of a wide range of diseases which manifest themselves in alocalized or “focal” manner, including cancers of the breast, brain,liver, and kidney. As explained herein, the disclosed apparatus uses anintracavity probe which will be particularly useful for focal diseaseswhich are accessible to a transesophageal, laparoscopic or transvaginalprobe. Such diseases include esophageal cancer, cancer in the tracheaand urethra, ulcers in the stomach and duodenum, and pancreatic cancer.Moreover, a transvaginal probe according to the present invention willprovide a minimally invasive sterilization procedure on an outpatientbasis, as well as therapy for fibroids, and endometrial ablation.Additionally, in the case of a transducer with multiple focal lengths,blood vessels may be selectively targeted to effect coagulation andcauterization of internal bleeding.

As used herein the term “HIFU Therapy” is defined as the provision ofhigh intensity focused ultrasound to a portion of tissue at or proximateto a focus of a transducer. It should be understood that the transducermay have multiple foci and that HIFU Therapy is not limited to a singlefocus transducer, a single transducer type, or a single ultrasoundfrequency. As used herein the term “HIFU Treatment” is defined as thecollection of one or more HIFU Therapies. A HIFU Treatment may be all ofthe HIFU Therapies administered or to be administered, or it may be asubset of the HIFU Therapies administered or to be administered. As usedherein the term “HIFU System” is defined as a system that is at leastcapable of providing a HIFU Therapy.

Various methods have been used to determine whether the above mentionedtreatments are successful. The gold standard test is a biopsy of thetissue. However, other post treatment tests have been used in an attemptto determine the success of the above treatments. In the case oftreating prostate tissue for prostate cancer, one such test is the levelof prostate-specific antigen (PSA) in the blood at various timessubsequent to testing. PSA is a serine protease normally produced in theprostate. However, both of these methods, biopsy and PSA monitoring, areconducted after the HIFU Treatment has been completed, typically manymonths later, and thus are not helpful in assisting the physician indetermining either prior to the HIFU Treatment or during the HIFUTreatment the potential success of the HIFU Treatment.

Further, it is known to treat the whole prostate and to monitor thetemperature of the prostate during treatment to determine if thetemperature rise is sufficient to cause cell death. One method tomonitor the temperature rise is to position a thermocouple in theprostate, but this is an invasive procedure. Another method to monitortemperature rise is to perform the HIFU Treatment while the patient ispositioned within an MRI device. The MRI device is used to monitor thetemperature rise in the prostate.

A need exists for a more reliable method of determining the success of aHIFU Treatment of a given treatment region. Additionally, a need existsfor determining the success of a HIFU Treatment which does not subjectthe patient to invasive testing methods including biopsy and blooddraws. Further, a need exists for a cost-effective, reliable method ofdetermining the success of a HIFU Treatment after the completion of aHIFU Treatment, during a HIFU Treatment and/or prior to the commencementof a HIFU Treatment.

It is known that during the treatment of the prostate air bubblesbetween the probe and the rectal wall, such as between an acousticmembrane of the probe and the rectal wall, or calcification in therectal wall may block the propagation of HIFU energy from beingadequately delivered to the treatment site. Further, the application ofHIFU energy in the presence of such an acoustic obstruction may resultin damage to the rectal wall, such as a recto-urethral fistula.Traditionally, the physician is trained to observe multiplereverberations from an ultrasound image as an indication of an acousticobstruction. A need exists for an automated method of detecting acousticobstructions proximate to the rectal wall to avoid unwanted damage tothe rectal wall.

In an exemplary embodiment of the present invention, a method ofproviding treatment to a treatment region of tissue is provided. Themethod comprising the steps of: planning a proposed HIFU Treatment ofthe treatment region; and determining prior to commencement of theproposed HIFU Treatment whether the proposed HIFU Treatment should besuccessful in treating the tissue of the treatment region. In anexample, the determination of whether the proposed HIFU Treatment shouldbe successful is based at least on an energy density of the energyplanned to be deposited into the treatment region. In another example,the step of determining prior to commencement of the proposed HIFUTreatment whether the proposed HIFU Treatment should be successful intreating the tissue of the treatment region, comprises the steps of:calculating an energy density for the proposed HIFU Treatment; comparingthe calculated energy density to a reference energy density; indicatingthat the proposed HIFU Treatment should be successful if the calculatedenergy density is greater than or equal to the reference energy density;and presenting the proposed HIFU Treatment to a reviewer for review ifit is indicated that the proposed HIFU Treatment should be successful.In a further example, the step of planning the proposed HIFU Treatmentof the treatment region comprises the steps of: generating arepresentation of the tissue; indicating a location of the treatmentregion on the representation of the tissue; and providing a plurality ofproposed treatment sites within the treatment region, each of theproposed treatment sites having a proposed amount of energy to bedeposited thereto. In one exemplary variation, the step of determiningprior to commencement of the proposed HIFU Treatment whether theproposed HIFU Treatment should be successful in treating the tissue ofthe treatment region, comprises the steps of: calculating an energydensity for the proposed HIFU Treatment; comparing the calculated energydensity to a reference energy density; indicating that the proposed HIFUTreatment should be successful if the calculated energy density isgreater than or equal to the reference energy density; and presentingthe proposed HIFU Treatment to a reviewer for review if it is indicatedthat the proposed HIFU Treatment should be successful.

In another exemplary embodiment of the present invention, a method ofdetermining the success of a given HIFU Treatment of a given treatmentregion is provided. The method comprising the steps of: providing a HIFUSystem to administer the given HIFU Treatment, the HIFU System includinga transducer configured to provide a HIFU Therapy to a plurality oftreatment sites and a controller configured to control the position andoperation of the transducer; calculating an energy density for the givenHIFU Treatment; comparing the calculated energy density to a referenceenergy density; and classifying the given HIFU Treatment as a successfulHIFU Treatment based on the calculated energy density being greater thanor equal to the reference energy density. In an example, the treatmentregion includes at least two treatment sub-portions, each treatmentsub-portion including a subset of the plurality of treatment sites. Inanother example, the HIFU Treatment is a proposed HIFU Treatment and thestep of calculating the energy density for the proposed HIFU Treatmentincludes the steps of: estimating an amount of energy to be deposited ateach of the plurality of treatment sites; summing the amount of energyto be deposited at each of the plurality of treatment sites; anddividing the summed amount of energy to be deposited by one of a volumeof the treatment region and a mass of the treatment region. In anexemplary variation, the method further comprises the steps of:preventing the HIFU Treatment from commencing if the calculated energydensity is less than the reference energy density; and providing anoverride option whereby the reviewer may request that the HIFU Treatmentcommence even though the calculated energy density is less than thereference energy density. In a further example, the HIFU Treatment is acurrent HIFU Treatment and the step of calculating the energy densityfor the current HIFU Treatment includes the steps of: estimating anamount of energy deposited at each of the plurality of treatment siteswhich have received HIFU Therapy; estimating an amount of energy to bedeposited at each of the plurality of treatment sites which have yet toreceive HIFU Therapy; summing the amount of energy deposited at each ofthe plurality of treatment sites which have received HIFU Therapy andthe amount of energy to be deposited at each of the plurality oftreatment sites which have yet to receive HIFU Therapy; and dividing thesummed amount of energy by one of a volume of the treatment region and amass of the treatment region. In an exemplary variation, the methodfurther comprises the step of: preventing the HIFU Treatment fromprogressing if the calculated energy density is less than the referenceenergy density; and providing an override option whereby the reviewermay request that the HIFU Treatment progress even though the calculatedenergy density is less than the reference energy density. In still afurther example, the HIFU Treatment is a completed HIFU Treatment andthe step of calculating the energy density for the completed HIFUTreatment includes the steps of: estimating an amount of energydeposited at each of the plurality of treatment sites; summing theamount of energy deposited at each of the plurality of treatment sites;and dividing the summed amount of energy deposited by one of a volume ofthe treatment region and a mass of the treatment region.

In a further exemplary embodiment of the present invention, an apparatusfor treating tissue is provided. The apparatus comprising: a transducerwhich is positionable proximate to the tissue, the transducer beingconfigured to emit ultrasound energy and to sense ultrasound energy; apositioning member coupled to the transducer and configured to positionthe transducer; and a controller operably coupled to the transducer andto the positioning member. The controller being configured to positionthe transducer with the positioning member and to operate the transducerin an imaging mode wherein images of the tissue are obtained fromultrasound energy sensed by the transducer and in a therapy mode whereina plurality of treatment sites are treated with a HIFU Therapy with thetransducer. The controller being further configured to plan a HIFUTreatment of a treatment region of the tissue to determine prior tocommencement of the HIFU Treatment whether the HIFU Treatment should besuccessful in treating the tissue of the treatment region based on anenergy density of the energy planned to be deposited into the treatmentregion. In an example, the controller is further configured to monitorthe HIFU Treatment as the HIFU Treatment progresses to determine whetherthe HIFU Treatment should be successful in treating the tissue of thetreatment region based on an amount of energy deposited into thetreatment region and an amount of energy planned to be deposited in thetreatment region. In another example, the apparatus further comprises adisplay operably coupled to the controller, the controller beingconfigured to present the images of the tissue on the display and toprovide a visual cue on the display of whether the planned HIFUTreatment should be successful in treating the tissue based on theamount of energy planned to be deposited into the treatment region andthe amount of energy deposited in the treatment region. In a furtherexample, the HIFU Treatment should be successful if the energy densityis at least equal to a reference energy density.

In yet a further exemplary embodiment of the present invention, acomputer-readable medium is provided. The computer readable mediumproviding instructions for directing a processor to: receive imageinformation from a transducer; generate at least one image from thereceived image information; determine a treatment region based on thereceived image information; plan a HIFU Treatment of at least a portionof the treatment region, the HIFU Treatment including a plurality oftreatment sites; calculate an energy density corresponding to theplanned HIFU Treatment; provide an indication of whether the plannedHIFU Treatment is likely to be successful based on the energy density;and control the transducer to conduct the planned HIFU Treatment. In anexample, the instructions further direct the processor to prevent theplanned HIFU Treatment from commencing if the planned HIFU Treatment isnot likely to be successful based on the energy density. In anotherexample, the instructions further direct the processor to monitor theplanned HIFU Treatment as the planned HIFU Treatment progresses and topermit a modification to the planned HIFU Treatment. In an exemplaryvariation, the instructions further direct the processor to calculate anupdated energy density corresponding to the planned HIFU Treatment withthe modification and to provide an updated indication of whether theplanned HIFU Treatment with the modification is likely to be successfulbased on the updated energy density. In another exemplary variation, theinstructions further direct the processor to prevent a furtherprogression of the planned HIFU Treatment with the modification if theupdated energy density does not indicate that the planned HIFU Treatmentwith the modifications is likely to be successful. In a further example,the planned HIFU Treatment is likely to be successful if the energydensity is at least equal to a reference energy density. In still afurther example, the energy density is calculated by the steps of:estimating an amount of energy to be deposited at each of the pluralityof treatment sites; summing the amount of energy to be deposited at eachof the plurality of treatment sites; and dividing the summed amount ofenergy to be deposited by one of a volume of the treatment region and amass of the treatment region.

In still a further exemplary embodiment of the present invention, amethod of providing treatment to a treatment region of tissue with aHIFU Treatment, the HIFU Treatment including the provision of HIFUTherapy at spaced apart intervals to a plurality of treatment siteswithin the treatment region, is provided. The method comprising thesteps of: driving the HIFU Treatment to generate a focal hyperechoicfeature for a given treatment site; and maintaining the HIFU Treatmentat a level to maintain the generation of subsequent focal hyperechoicfeatures at subsequent treatment sites. In one example, the methodfurther comprises the step of pausing the HIFU Treatment if a non-focalhyperechoic feature is generated. In an exemplary variation, the methodfurther comprises the step of reducing the total acoustic power forsubsequent treatment sites of the HIFU Treatment if a non-focalhyperechoic feature is generated which migrates from the respectivefocal zone.

In yet another exemplary embodiment of the present invention, a methodof providing treatment to a treatment region of tissue with a HIFUTreatment, the HIFU Treatment including the provision of HIFU Therapy atspaced apart intervals to a plurality of treatment sites within thetreatment region, is provided. The method comprising the steps of:distinguishing between a focal hyperechoic feature and a non-focalhyperechoic feature; continuing the HIFU Treatment upon the observanceof the focal hyperechoic feature; and pausing the HIFU Treatment uponthe observance of the non-focal hyperechoic feature. In an example, thestep of distinguishing between a focal hyperechoic feature and anon-focal hyperechoic feature includes the steps of: generating apost-treatment image of a first treatment site; comparing a region ofinterest of the treatment region in the post-treatment image to theregion of interest of the treatment region in a pre-treatment image;classifying the region of interest as containing a hyperechoic featurebased on the comparison of the region of interest of the treatmentregion in the post-treatment image and the pre-treatment image; andcomparing a location of the region of interest to a location of thetreatment site, wherein the hyperechoic feature is classified as a focalhyperechoic feature if the location of the region of interest generallycoincides with the location of the treatment site.

In still another exemplary embodiment of the present invention, anapparatus for treating tissue is provided. The apparatus comprising: aprobe including an acoustic membrane covering at least a portion of theprobe and a transducer positioned behind the acoustic membrane, thetransducer being configured to emit ultrasound energy and to senseultrasound energy; and a controller operably coupled to the transducer,the controller being configured to operate the transducer in an imagingmode wherein at least one image of the tissue is obtained fromultrasound energy sensed by the transducer and in a therapy mode whereina plurality of treatment sites are treated with a HIFU Therapy with thetransducer. The controller being further configured to detect thepresence of an acoustic obstruction adjacent the acoustic membrane bydetecting a repetitive pattern based on the at least one image of thetissue. In an example, the controller is further configured to preventoperation of the transducer in therapy mode based on a detection of anacoustic obstruction.

In a yet still a further exemplary embodiment of the present invention,a method of treating tissue in a treatment region is provided. Themethod comprising the steps of: imaging the treatment region with anultrasound transducer; automatically detecting an acoustic obstructionproximate to the ultrasound transducer; and preventing the commencementof a HIFU Treatment based upon the detection of the acoustic obstructionproximate to the ultrasound transducer. In an example, the step ofdetecting the acoustic obstruction comprises the steps of: analyzing aportion of an image for a repetitive pattern, and determining thepresence of the acoustic obstruction based on the presence of therepetitive pattern in the portion of the image. In an exemplaryvariation, the transducer is positioned within a probe behind anacoustic membrane of the probe and wherein the step of analyzing aportion of the image for a repetitive pattern comprises the steps of:analyzing a first portion of the image at about a position correspondingto the acoustic membrane and the tissue to determine if a firstintensity characteristic associated with the first portion meets orexceeds a first upper threshold; analyzing a second portion of the imageat about 1.5 times the position corresponding to the acoustic membraneand the tissue to determine if a second intensity characteristicassociated with the second portion is below a first lower threshold; andanalyzing a third portion of the image at about twice the positioncorresponding to the acoustic membrane and the tissue to determine if athird intensity characteristic associated with the third portion meetsor exceeds a second upper threshold.

In yet still another exemplary embodiment of the present invention, amethod of treating tissue in a treatment region with a HIFU Treatment isprovided. The method comprising the steps of: initiating a HIFU Therapyto treat a portion of the tissue with an ultrasound transducer;obtaining an image of the treatment region subsequent to attempting totreat the portion of the tissue with HIFU Therapy; automaticallydetecting an acoustic obstruction proximate to the ultrasoundtransducer; pausing the HIFU Treatment. In an example, the step ofdetecting the acoustic obstruction comprises the steps of: analyzing aportion of an image for a repetitive pattern, and determining thepresence of the acoustic obstruction based on the presence of therepetitive pattern in the portion of the image. In an exemplaryvariation, the transducer is positioned within a probe behind anacoustic membrane of the probe and wherein the step of analyzing aportion of the image for a repetitive pattern comprises the steps of:analyzing a first portion of the image at about a position correspondingto the acoustic membrane and the tissue to determine if a firstintensity characteristic associated with the first portion meets orexceeds a first upper threshold; analyzing a second portion of the imageat about 1.5 times the position corresponding to the acoustic membraneand the tissue to determine if a second intensity characteristicassociated with the second portion is below a first lower threshold; andanalyzing a third portion of the image at about twice the positioncorresponding to the acoustic membrane and the tissue to determine if athird intensity characteristic associated with the third portion meetsor exceeds a second upper threshold.

Additional features of the present invention will become apparent tothose skilled in the art upon consideration of the following detaileddescription of the illustrative embodiments exemplifying the best modeof carrying out the invention as presently perceived.

BRIEF DESCRIPTION OF THE DRAWINGS

The detailed description of the drawings particularly refers to theaccompanying figures in which:

FIG. 1 is schematic view of an exemplary HIFU System of the presentinvention, the HIFU System being capable of imaging the tissue of thepatient and to provide HIFU Therapy to at least a portion of the tissueat or proximate to a focus of a transducer of the HIFU System;

FIG. 2 is an exemplary embodiment of the HIFU System of FIG. 1;

FIG. 3A is a representation of a transverse or sector view of theprostate and rectum of the patient along with the probe and thetransducer of the HIFU System of FIG. 1;

FIG. 3B is a representation of a longitudinal or linear view of theprostate and rectum of the patient along with the probe and thetransducer of the HIFU System of FIG. 1;

FIG. 3C is a representation of a transverse or sector view of theprostate of the patient wherein the whole prostate corresponds to thetreatment region, the treatment region illustratively including sixtreatment segments;

FIG. 3D is a representation of a longitudinal or linear view of theprostate of the patient wherein the whole prostate corresponds to thetreatment region, the treatment region illustratively including sixtreatment segments;

FIG. 4 is an exemplary process for an exemplary HIFU Treatment;

FIG. 5 is a Student's t-test of a calculated density of the energydeposition for a sample of patients which had biopsies subsequent to aHIFU Treatment, the density of the energy deposition being calculatedwith the assumption that the intensity attenuation coefficient is equalto infinity;

FIG. 6 is a Student's t-test of a calculated density of the energydeposition for a sample of patients which had biopsies subsequent to aHIFU Treatment, the density of the energy deposition being calculatedwith the assumption that the intensity attenuation coefficient is equalto 0.64 Np/cm;

FIG. 7 is an exemplary receiver operator characteristic curve (ROC) forthe density of the energy depositions and biopsy results shown in FIGS.5 and 6, the ROC in this case provides a measure of the ability of atest to determine if the density of the energy deposition represents adiseased or not diseased state;

FIGS. 8A and 8B illustratively provide an exemplary method of operationof the HIFU System of FIG. 1 wherein the HIFU System analyzes a plannedor proposed HIFU Treatment, a current HIFU Treatment, and/or a completedHIFU Treatment to predict the success of such HIFU Treatment;

FIGS. 9A and 9B illustratively describe various hyperechoic features,including focal hyperechoic features and non-focal hyperechoic features;

FIG. 10 illustrates exemplary focal hyperechoic features;

FIG. 11 illustrates exemplary non-focal hyperechoic features;

FIG. 12 illustratively provides an exemplary method of tailoring thetreatment of tissue based on the presence of hyperechoic features;

FIG. 13A illustratively provides an exemplary method of monitoring foracoustic obstructions proximate to the transducer relative to thetreatment region and for tailoring the treatment of tissue based on thepresence of the acoustic obstructions;

FIG. 13B illustratively provides an exemplary method of monitoring foracoustic obstructions by monitoring for repetitive acoustic features;

FIG. 14A is an exemplary line image of a portion of a treatment regionincluding the rectal wall and prostate and not including an acousticobstruction proximate to the transducer;

FIG. 14B is an exemplary line image of a portion of a treatment regionincluding the rectal wall and prostate and including an acousticobstruction proximate to the transducer;

FIG. 15A is a representation of the rectum of the patient along with theprobe, the transducer, and an acoustic membrane covering a portion ofthe probe of the HIFU System of FIG. 1;

FIG. 15B is a representation of the view of FIG. 15A wherein an acousticobstruction is positioned proximate to the transducer, illustrativelybetween the acoustic membrane and the rectal wall; and

FIG. 16 is an exemplary method for detecting and classifying hyperechoicfeatures.

DETAILED DESCRIPTION OF THE DRAWINGS

An exemplary HIFU System 100 is shown in FIG. 1. HIFU System 100includes a probe 102 having a transducer member 104, a positioningmember 106, a controller 108 operably coupled to probe 102 and thepositioning member 106, a user input device 110 (such as keyboard,trackball, mouse, and/or touch screen), and a display 112. Probe 102 isoperably connected to controller 108 through positioning member 106.However, as indicated by line 105 probe 102 may be directly connectedwith controller 108. Positioning member 106 is configured to linearlyposition transducer member 104 along directions 113, 114 and toangularly position transducer member 104 in directions 115, 116.

Transducer member 104 is positioned generally proximate to a region oftissue 10. In the case of the prostate, transducer 104 is positionedgenerally proximate to the prostate by the transrectal insertion ofprobe 102. Transducer member 104 is moved by positioning member 106 andcontrolled by controller 108 to provide imaging of at least a portion oftissue 10 including at least one treatment region 12 and to provide HIFUTherapy to portions of the tissue within at least one treatment region12. As such, HIFU System 100 may operate in an imaging mode wherein atleast a portion of tissue 10 may be imaged and in a therapy mode whereinHIFU Therapy is provided to portions of tissue 10 within at least onetreatment region. As stated herein, treatment region 12 is defined asone or more portions of tissue which are to be treated during a HIFUTreatment. Treatment region 12 is illustratively shown as a continuousregion. However, a treatment region might involve two or more distinctregions. In one example, illustrated in FIGS. 3C and 3D, treatmentregion 12 includes a plurality of treatment sub-portions, illustrativelytreatment segments 340 a-f.

In one embodiment, transducer member 104 is a single crystal two elementtransducer. An exemplary transducer is disclosed in U.S. Pat. No.5,117,832, the disclosure of which is expressly incorporated herein byreference. In a preferred embodiment, transducer 104 is capable ofproviding imaging of at least a portion of tissue 10 and of providingHIFU Therapy to at least a portion of tissue 10 within treatment region12.

However, the present invention is not limited to the type of transducerimplemented. On the contrary, various transducer geometries having asingle focus or multiple foci and associated controls may be usedincluding transducers which are phased arrays, such as the transducersdisclosed in pending U.S. patent application Ser. No. 11/070,371, filedMar. 2, 2005, titled “Ultrasound Phased Arrays,” Attorney Docket No.INT-P001-01, the disclosure of which is expressly incorporated herein byreference. Additional exemplary transducers and associated controls aredisclosed in U.S. Pat. No. 5,762,066; U.S. Abandoned patent applicationSer. No. 07/840,502 filed Feb. 21, 1992; Australian Patent No.5,732,801; Canadian Patent No. 1,332,441; Canadian Patent No. 2,250,081;U.S. Pat. No. 5,036,855; U.S. Pat. No. 5,492,126; U.S. Pat. No.6,685,640, each of which is expressly incorporated herein by reference.

In one embodiment, a portion of probe 102 is covered by an acousticmembrane 103. Acoustic membrane 103 is an expandable membrane whoseoverall size is increased by placing a fluid on an interior of acousticmembrane 103. In one embodiment, the fluid is water or a generallyacoustic transparent material and is provided by a reservoir or achiller. The fluid may be used to remove heat from proximate totransducer 104 as well as expanding acoustic membrane 103. In oneembodiment, acoustic membrane 103 is expanded such that it contacts orgenerally is adjacent to the surrounding tissue, such as rectal wall323, as shown in FIG. 15A. In one embodiment, acoustic membrane 103 is acondom placed over a tip of probe 102, sealed with o-rings, and filledwith water. Exemplary acoustic membranes and details of their operationin relation to respective other portions of exemplary HIFU Systems areprovided in U.S. Pat. No. 5,762,066, U.S. Pat. No. 5,993,389, and U.S.Provisional Patent Application Ser. No. 60/686,499, filed Jun. 1, 2005,the disclosures each of which are expressly incorporated by referenceherein.

In one embodiment, controller 108 is configured to execute one or moreof the methods discussed herein. In one embodiment, at least a portionof each method executed by controller 108 is provided as a portion ofsoftware 109.

Referring to FIG. 2, an exemplary HIFU System 200 is shown, theSonablate® 500 HIFU System available from Focus Surgery, Inc., locatedat 3940 Pendleton Way, Indianapolis, Ind. 46226. HIFU System 200includes a console 202 which houses or supports a controller (notshown), such as a processor and associated software; a printer 204 whichprovides hard copy images of tissue 10 and/or reports (see FIG. 8B); auser input device 206 such as a keyboard, trackball, and/or mouse; and adisplay 208 for displaying images of tissue 10 and software options to auser, such as a color display. Further, shown is a probe 210 whichincludes a transducer member (not shown), and a positioning member (notshown). Also shown is an articulated probe arm 212 which is coupled toconsole 202. Articulated probe arm 212 orients and supports probe 210. Achiller 214 is also shown. Chiller 214, in one embodiment, provides awater bath with a heat exchanger for the transducer member of probe 210to actively remove heat from the transducer member during a HIFUTreatment.

Further details of suitable HIFU Systems which may be modified toexecute the methods described herein are disclosed in U.S. Pat. No.4,084,582; U.S. Pat. No. 4,207,901; U.S. Pat. No. 4,223,560; U.S. Pat.No. 4,227,417; U.S. Pat. No. 4,248,090; U.S. Pat. No. 4,257,271; U.S.Pat. No. 4,317,370; U.S. Pat. No. 4,325,381; U.S. Pat. No. 4,586,512;U.S. Pat. No. 4,620,546; U.S. Pat. No. 4,658,828; U.S. Pat. No.4,664,121; U.S. Pat. No. 4,858,613; U.S. Pat. No. 4,951,653; U.S. Pat.No. 4,955,365; U.S. Pat. No. 5,036,855; U.S. Pat. No. 5,054,470; U.S.Pat. No. 5,080,102; U.S. Pat. No. 5,117,832; U.S. Pat. No. 5,149,319;U.S. Pat. No. 5,215,680; U.S. Pat. No. 5,219,401; U.S. Pat. No.5,247,935; U.S. Pat. No. 5,295,484; U.S. Pat. No. 5,316,000; U.S. Pat.No. 5,391,197; U.S. Pat. No. 5,409,006; U.S. Pat. No. 5,443,069, U.S.Pat. No. 5,470,350, U.S. Pat. No. 5,492,126; U.S. Pat. No. 5,573,497,U.S. Pat. No. 5,601,526; U.S. Pat. No. 5,620,479; U.S. Pat. No.5,630,837; U.S. Pat. No. 5,643,179; U.S. Pat. No. 5,676,692; U.S. Pat.No. 5,840,031; U.S. Pat. No. 5,762,066; U.S. Pat. No. 6,685,640; U.S.Abandoned patent application Ser. No. 07/840,502 filed Feb. 21, 1992;Australian Patent No. 5,732,801; Canadian Patent No. 1,332,441; CanadianPatent No. 2,250,081; U.S. patent application Ser. No. 11/070,371, filedMar. 2, 2005, titled “Ultrasound Phased Arrays,” Attorney Docket No.INT-P001-01; U.S. Provisional Patent Application No. 60/568,556, filedMay 6, 2004, titled “Treatment of Spatially Oriented Disease with aSingle Therapy, Imaging, and Doppler Ultrasound Transducer,” AttorneyDocket No. 15849-0002; PCT Patent Application Serial No. US2005/015648,filed May 5, 2005, designating the US, titled “Method and Apparatus forthe Selective Treatment of Tissue”, Attorney Docket No. FOC-P001-01, thedisclosures each of which is expressly incorporated herein by reference.

As explained herein, HIFU System 100 is configured to provide apredictor of the success of a given HIFU Treatment during the planningportion of the given HIFU Treatment, during the performance of the HIFUTreatment, and/or subsequent to the completion of the HIFU Treatment. Inone exemplary embodiment, controller 108 includes software 109 whichwhen executed determines whether the given HIFU Treatment was likelysuccessful or will likely result in a successful treatment. Further,software 109 controls the operation of HIFU System 100 including theimaging, planning, and treatment operations.

Referring to FIGS. 3A-3D and FIG. 4, an overview of an HIFU Treatmentwith HIFU System 100 is explained. Referring to FIG. 4, an exemplaryHIFU Treatment 300 includes the imaging of the treatment region and/orsurrounding tissue, as represented by block 302; the planning of a HIFUTreatment, as represented by block 304; and the performance of the HIFUTreatment, as represented by block 306.

In a first exemplary embodiment, the treatment region and surroundingtissue is imaged with HIFU System 100 using conventional ultrasoundtechniques. HIFU System 100 generates and stores a plurality of 2-Dimages of tissue 10 including treatment region 12. In one example, HIFUSystem 100 generates and stores a plurality of transverse or sectorimages about every 3 mm along the treatment region (as represented bylines 310 a-c in FIG. 3B) and generates and stores a plurality oflongitudinal or linear images about every 3° (as represented by lines312 a-g in FIG. 3A). In other examples, different spacing of thetransverse and longitudinal images are used.

As used herein, the term “treatment region” is defined as one or moreportions of tissue which are to be treated during a HIFU Treatment. Ingeneral, treatment region is used to describe the overall area beingtreated during a HIFU Treatment. However, treatment region may also beused to describe one or more sub-regions of the overall area beingtreated, such as one or more treatment segment(s) and/or one or moretreatment site(s).

Referring to FIGS. 3A and 3B, in the application of treating prostatecancer, tissue 10 includes the prostate 314 of the patient, the prostate314 having a capsule 316 and cancerous tissue 318 located within theinterior of capsule 316. As is known, prostate 314 surrounds urethra 320and is positioned proximate to the rectum 322 having a rectal wall 323.Rectum 322 receives probe 102 of HIFU System 100 such that transducer104 is positioned proximate to prostate 314. Transducer 104 is used toimage tissue 10 as represented by lines 310 a-c in FIG. 3B (transverseimages) and by lines 312 a-g in FIG. 3A (longitudinal images). Further,transducer 104 is used to provide HIFU Therapy to tissue 10,illustratively to tissue 324 in FIG. 3B.

Based on the 2-D images generated and stored, the physician is able toplan the HIFU Treatment, as represented by block 304 in FIG. 4. In oneembodiment, the physician examines an image on display 112 and with userinput device 110 marks the boundaries of a treatment segment 328, asrepresented by endpoints 330 a,b and line 332 in FIG. 3A. Based ontreatment segment 328, HIFU System 100 generates a plurality oftreatment sites or zones which generally correspond to the intersectionof treatment segment 328 and imaged locations of tissue 10 (tissue whichhas at least one of or preferably both of a corresponding transverseimage and a corresponding longitudinal image). An exemplary treatmentsite 334 d is shown in FIGS. 3A and 3B and is imaged in both images 310a (generally corresponding to the plane of FIG. 3A) and image 312 d(generally corresponding to the plan of FIG. 3B). Treatment segments 328may be generated on either transverse images (300 a-c) and/orlongitudinal images (312 a-g). In alternative embodiments, treatmentsites do not correspond to imaged locations of tissue.

By restricting treatment sites 334 to imaged tissue locations, thephysician is able to see images of the representative tissue prior toHIFU Therapy and immediately following HIFU Therapy or at further timessubsequent to HIFU Therapy. Thus, the physician may compare the treatedtissue to its pre-HIFU state. Also, the physician is able to monitor thetreatment site and surrounding tissue for the hyperechoic features asdescribed herein.

As stated herein, in one embodiment it is desirable to observe focalhyperechoic features at a treatment site subsequent to treatment withHIFU Therapy. Further, it is generally undesirable to observe non-focalhyperechoic features subsequent to treatment with HIFU Therapy. As usedherein a focal hyperechoic feature is defined as a hyperechoic featurewhich is generally confined to a focal zone of a treatment site. As usedherein a non-focal hyperechoic feature is defined as a hyperechoicfeature which is generally treatment site specific and migrates from thefocal zone of the treatment site, such as towards the transducer.

In one embodiment, a plurality of images, such as a plurality oftransverse images are simultaneously displayed on display 112, such thatthe physician may plan treatment segments on multiple images while stillviewing related images. In one embodiment, display 112 is capable ofdisplaying the number of images which correspond to the complete linearmovement of transducer 104. In one example, transducer 104 may belinearly moved a range of about 45 mm and tissue 10 is imaged at 3 mmintervals. Thus, fifteen transverse images are displayed on display 112at the same time. In general, the fifteen transverse images spaced atabout 3 mm provide images of the entire prostate.

Referring to FIGS. 3C and 3D, exemplary treatment segments 340 a-f areshown. Treatment segments 340 a-f cover the entire prostate 314. Eachsegment is defined as a region in the treatment zone including aplurality of treatment sites. In one embodiment, a HIFU Treatmentconsists of multiple treatment segments positioned such that thesubstantially whole prostate is within the treatment region.

During a HIFU Treatment, treatment segments 340 a-f are treated insuccessive order. For a given treatment segment, transducer 104 is movedto coincide with the treatment segment and the focal length of thetransducer is chosen. In one example, transducer 104 has two focallengths, 30 mm and 40 mm. In one embodiment, treatment sites in a giventreatment segment are treated with HIFU Therapy by rotating thetransducer transverse to the probe axis and then treating all of thesites at that angular or sector position by systematically translatingtransducer 104 from one end of a given treatment segment to the otherend of the treatment segment in one of directions 113, 114. Thissystematic treatment is then repeated for each angular or sectorposition within the treatment segment.

HIFU Therapy greatly changes the acoustic (physical) properties oftissue. Thus, in one embodiment the treatment segments farthest from thetransducer (anterior side) are treated first with the treatmentprogressing towards the position of the probe (posterior side). There isvery little change in the value of the TAP setting for the treatmentsites within a given treatment segment. In one example, a HIFU Therapyis provided for 3 seconds at an excitation frequency of about 4 MHzplus/minus about 50 KHz. In addition, the focal distance is the same andthe tissue path is similar for all treatment sites within a treatmentsegment. In one example, to limit the change in the physical propertiesof the tissue between the transducer member 104 of probe 210 and thetreatment segment, sector positions as demonstrated in FIG. 3A bytreatment sites 334 a-g within a given treatment segment are not treatedsuccessively, but rather in a spaced manner. In the linear direction fora given treatment segment, the order of treatment sites is generallysuccessive. Referring to FIG. 3B, treatment sites are generally treatedin the following order 334 i, 334 h, and 334 d. Referring to FIG. 3A,the order of the sector positions when treating a treatment segment isinterleaved in the following order: 334 d; 334 f, 334 b; 334 e; 334 c;334 g; and 334 a. In another example, the sector position order may bealternating from inside of the treatment segment towards the outside ofthe treatment segment resulting in the following order: 334 d; 334 e;334 c; 334 f, 334 b; 334 g; and 334 a. In another example, the sectorposition order may be alternating from outside of the treatment segmenttowards the inside of the treatment segment resulting in the followingorder: 334 a; 334 g; 334 b; 334 f, 334 c; 334 e; and 334 d. In anotherexample, the sector positions are ordered successively from 334 a-g.

In one embodiment, a three-dimensional model of tissue 10 is construedbased on the plurality of 2-D images of tissue 10. In one example, thethree-dimensional model is construed based on the 2-D images of tissue10 and/or 3-D images of tissue 10 and Doppler imaging of tissue 10.Example tissue components modeled include one or more of prostate 314,prostate capsule 316, urethra 320, rectum 322, and rectal wall 323. Anexplanation of exemplary methods and apparatus to calculate athree-dimensional model of the prostate and/or other tissue componentsare disclosed in U.S. Provisional Patent Application No. 60/568,556,filed May 6, 2004, titled “Treatment of Spatially Oriented Disease witha Single Therapy, Imaging, and Doppler Ultrasound Transducer,” AttorneyDocket No. 15849-0002 and PCT Patent Application Serial No.US2005/015648, filed May 5, 2005, designating the US, titled “Method andApparatus for the Selective Treatment of Tissue”, Attorney Docket No.FOC-P001-01, the disclosures each of which is expressly incorporatedherein by reference.

In one embodiment, HIFU System 100 generates a HIFU Treatment plan totreat substantially all of prostate 314, the HIFU Treatment plan beingbased in part on the three-dimensional model of prostate 314 and/oradditional tissue components. Exemplary methods and apparatus togenerate the HIFU Treatment plan are disclosed in U.S. ProvisionalPatent Application No. 60/568,556, filed May 6, 2004, titled “Treatmentof Spatially Oriented Disease with a Single Therapy, Imaging, andDoppler Ultrasound Transducer,” Attorney Docket No. 15849-0002 and PCTPatent Application Serial No. US2005/015648, filed May 5, 2005,designating the US, titled “Method and Apparatus for the SelectiveTreatment of Tissue”, Attorney Docket No. FOC-P001-01, the disclosureseach of which is expressly incorporated herein by reference.

In one exemplary embodiment, a method for predicting the success of aHIFU Treatment is based on the density of energy deposited(E_(Deposition)) to the tissue in the treatment region. In one example,the density of the energy deposition is obtained by dividing the totalenergy deposited within the tissue in the treatment region by the volumeof the treatment region (J/cm³). In another example, the density of theenergy deposition is obtained by dividing the total energy depositedwithin the tissue in the treatment region by the pre-treatment mass ofthe tissue in the treatment region (J/g). By using a density value afirst HIFU Treatment having a first treatment region size, such as forpatient A, may be easily compared to a second HIFU Treatment having adifferent second treatment region size, such as for patient B. As such,an exemplary density of the energy deposition (E_(Deposition)) may beobtained by dividing the energy deposited to the tissue by the mass ofthe treatment region; expressed as: $\begin{matrix}{E_{Deposition} = \frac{E}{M_{TreatmentRegion}}} & (1)\end{matrix}$wherein E_(Deposition) is the density of the energy deposition, E is theenergy deposited to the tissue in the treatment region andM_(TreatmentRegion) is the mass of the treatment region.

In an illustrated example, the prostate is being treated with a HIFUTreatment. In the illustrated example, substantially the whole prostateis being treated. As such, the size of the treatment region is generallyequal to the size of the prostate itself. The density of the energydeposition (E_(Deposition)) may be calculated by the following equation:$\begin{matrix}{E_{Deposition} = {\frac{\sum\limits_{{All}\quad{Sites}}\quad{\left( {1 - {\mathbb{e}}^{{- \alpha_{site}}L_{site}}} \right)A_{site}T\quad A\quad P_{site}t_{ON}}}{M_{prostate}}.}} & (2)\end{matrix}$wherein: TAP_(site) is the total acoustic power applied at eachtreatment site or zone; t_(ON) is the time duration that HIFU energy isbeing applied; A site is the attenuation arising from propagationthrough tissue before the HIFU Treatment site or zone; □_(site) is theintensity attenuation coefficient in Np/cm (Np=nepers) which accountsfor the energy absorbed by the acoustic wave within the treatment zone;L_(site) is the length of the treatment zone tissue path for eachtreatment site; and M_(prostate) is the measurement of the prostate masswhich is determined in part based on transrectal ultrasound imaging withthe HIFU System as explained herein.

The parameters L_(site), t_(on), and A_(site) may be either estimated orinferred based on the location of the treatment site and the parametersof the HIFU System. A_(site) may be determined from the followingequation: $\begin{matrix}{{A_{site} = {\prod\limits_{layer}\quad{\mathbb{e}}^{{- \alpha_{layer}}L_{layer}}}},} & (3)\end{matrix}$wherein

_(layer) and

_(layer) are the intensity attenuation coefficient and the layer lengthrespectively. For the example of treating the prostate (assuming thewhole prostate is the treatment region) A_(site) may be estimated to beequal to one if the rectal wall (FIG. 3B) is ignored and the waterbefore the prostate is approximated with an attenuation coefficient ofzero. (As stated herein, transducer 104 is within a water bath suppliedby chiller 214.) As such, the only parameters still requiring a methodof measurement or estimation are the total acoustic power applied ateach treatment site (TAP_(site)), the mass of the prostate(M_(prostate)), and the intensity attenuation coefficient at each site(α_(site)).

The intensity at the focus (I_(focus)) of the transducer being used fortreatment may be determined from the following equation: $\begin{matrix}{I_{focus} = {\frac{1}{f_{area}}T\quad A\quad P_{site}{\mathbb{e}}^{{- \alpha_{site}}L_{site}}}} & (4)\end{matrix}$wherein f_(area) is the area of the focus of the transducer, α_(site) isthe intensity attenuation coefficient in Np/cm which accounts for theenergy absorbed by the acoustic wave within the treatment zone; andL_(site) is the length of the treatment zone tissue path for eachtreatment site. As stated above L_(site) may be estimated from thelocation of the treatment site and the parameters of the HIFU System.f_(area) may be measured or estimated. TAP_(site) may be measured forthe transducer as a function of excitation energy with an acoustic powermeter, such as the UPM-DT-10 Ultrasound Power Meter available from OhmicInstruments Company, located in Easton, Md.

The mass of the prostate (M_(prostate)) may be calculated by multiplyingthe volume of the prostate by about 1.050 gm/cm³. However, as statedherein the volume of the prostate may be used to determine the densityof the energy deposition instead of the mass of the prostate. In oneembodiment, the volume of the prostate is estimated using a prolateellipsoid formula which is based on a normal untreated prostate shapeand is expressed asV_(prostate)=0.52W_(T)H_(AtOP)L_(L)  (5)wherein V_(prostate) is the volume of the prostate; W_(T) is thetransverse width; H top is the anterior to posterior height of theprostate; L_(L) is the longitudinal length of the prostate capsule. Thethree parameters W_(T), H_(AtoP), and L_(L) are measurable from the twodimensional transrectal ultrasound images of the prostate. In oneexample, the physician marks the locations of the treatment region bymarking on the two dimensional images the endpoints for the above threeparameters. Software 109 of HIFU System 100 then calculates the valuesfor each parameter and the value for V_(prostate). In one embodiment,software 109 of HIFU System 100 automatically locates the endpoints ofthe above three parameters and calculates the V_(prostate) for a givenprostate. Similarly looking at images of a prostate, a user may readilyindicate the endpoints for the above parameters and manually calculatethe volume of the prostate.

In another embodiment, the volume of the prostate is estimated bycalculating a three-dimensional model of the actual prostate from twodimensional transrectal ultrasound images. This method provides a moreaccurate volume of the prostate than the prolate ellipsoid formula. Anexplanation of exemplary methods and apparatus to calculate athree-dimensional model of the prostate and/or other tissue componentsare disclosed in U.S. Provisional Patent Application No. 60/568,556,filed May 6, 2004, titled “Treatment of Spatially Oriented Disease witha Single Therapy, Imaging, and Doppler Ultrasound Transducer,” AttorneyDocket No. 15849-0002 and PCT Patent Application Serial No.US2005/015648, filed May 5, 2005, designating the US, titled “Method andApparatus for the Selective Treatment of Tissue”, Attorney Docket No.FOC-P001-01, the disclosures each of which is expressly incorporatedherein by reference.

The tissue intensity attenuation coefficient, α_(site), varies as afunction of frequency. For acoustic energy being delivered to theprostate at about 4.0 MHz (site is about 0.64 Np/cm. Since all of theparameters of equation 2 may now be measured or estimated, the densityof the energy deposition may be calculated for a completed HIFUTreatment of the prostate, a current HIFU Treatment of the prostate,and/or a planned HIFU Treatment of the prostate. Further, since thedensity of the energy deposition (E_(Deposition)) is a density value, itis possible to compare a first HIFU Treatment to a second HIFU Treatmentregardless of the sizes of the respective treatment regions.

In order to evaluate the ability of the density of the energy deposition(E_(Deposition)) to function as a predictor of the success of a HIFUTreatment in the treatment of prostate cancer, data from a sample oftwenty patients was analyzed. Each of the patients had participated in aclinical trial at the Indiana University School of Medicine in Indianawherein each was treated for prostate cancer with the Sonablate® 500HIFU System. A biopsy of the prostate was analyzed at 180 days afterHIFU Treatment for nineteen of the participants (1 participant diedprior to 180 days of an unrelated myocardial infarction). A positivebiopsy was defined as a treatment failure and a negative biopsy wasdefined as a treatment success.

The density of the energy deposition (E_(Deposition)) was calculated foreach participant using two different values for α_(site) (α_(site)=∞ andα_(site)=0.64 Np/cm). Setting α_(site) to infinity is equivalent tostating that all of the HIFU energy is absorbed by the prostate. Foreach of the nineteen subjects and for both values of α_(site), the totalacoustic power (TAP) values for three sites (first site, center site,last site) within a given treatment segment were averaged and used asthe basis for the TAP value of all sites in the given treatment segment.t_(ON) for each site was 3 seconds. As discussed above A_(site) was setto one. The mass of the prostate (M_(prostate)) for each subject wasestimated using a prolate ellipsoid formula that is based on thenormal/untreated prostate shape.

For the case of assuming that α_(site) is equal to infinity, equation 2may be expressed as: $\begin{matrix}{E_{Deposition} = {\frac{\sum\limits_{{All}\quad{Sites}}\quad{T\quad A\quad P_{site}t_{ON}}}{M_{prostate}}.}} & (6)\end{matrix}$The density of the energy deposition (E_(Deposition)) for each patientwas calculated. The density of the energy deposition (E_(Deposition))for each patient is shown in FIG. 5. The density of the energydepositions are shown with the negative and positive biopsies inseparate columns. Referring to FIG. 5, a discernable spread is shownbetween the density of the energy deposition (E_(Deposition)) for thepatients that had a negative biopsy and for patients that had a positivebiopsy. The value indicated as p in FIG. 5 represents the probabilitythat the distribution of the density of the energy deposition resultsare the same for patients that had a negative biopsy and for patientsthat had a positive biopsy. If p is less than 0.05, the conclusion isthat there is a significant difference between the density of energydeposition results for the two groups of patients. Thus the result shownin FIG. 5 demonstrates that there is a 98.1% probability that thedensity of energy deposition is different for the two groups ofpatients.

For the case of assuming that α_(side)=0.64Np/cm, equation 2 is used tocalculate the density of the energy deposition (E_(Deposition)) for eachpatient. The differences in the density of the energy deposition(E_(Deposition)) for each patient is shown in FIG. 6. The density of theenergy depositions are shown with the negative and positive biopsies inseparate columns. Referring to FIG. 6, a significant difference isdemonstrated between the density of energy deposition (E_(Deposition))for patients that had a negative biopsy and for patients that had apositive biopsy. For the data shown in FIG. 6, the probability that thedensity of energy deposition is different for the two groups of patientsis 98.6%.

Both FIGS. 5 and 6 demonstrate that the density of the energy deposition(E_(Deposition)) appears to be a predictive factor in the ability todetermine the success or failure of a given HIFU Treatment of theprostate. In order to determine the ability of the density of the energydeposition as a deciding factor in determining the success or failure ofa given HIFU treatment, a receiver operator characteristic (ROC)analysis was applied for the nineteen patients discussed above and foreach of the intensity attenuation coefficient values (α_(site)). Forboth attenuation settings (α_(site)), the ‘gold standard’ test forcancer was the post-treatment 180 day biopsy result, whereas the testbeing measured by the ROC analysis is the density of the energydeposition (E_(Deposition)) given by equation (2) or equation (6) in thecase of α_(site) equal to infinity.

The first step in the ROC analysis is to obtain a data set that includesboth the test (density of the energy deposition) and the corresponding‘gold standard’ measure (biopsy of prostate). Then an array of decisionlevels are created that span the range of the test values (density ofthe energy deposition levels). A 2 by 2 table is created that followsthe template shown in Table 1. TABLE 1 Biopsy (Positive) Biopsy(Negative) E_(Deposition) True Positive (TP) False Positive (FP) (Lowerthan Threshold) E_(Deposition) False Negative (FN) True Negative (TN)(Higher than Threshold)In the template shown in Table 1, the columns represent the ‘goldstandard’ (Biopsy), while the rows represent the test (E_(Deposition)).From this table two key quantities may be defined: $\begin{matrix}{{Sensitivity} = \frac{TP}{\left( {{TP} + {FN}} \right)}} & (7) \\{{Specificity} = \frac{TN}{\left( {{FP} + {TN}} \right)}} & (8)\end{matrix}$

The sensitivity is a measure of how well the test detects the parametersought, in this case subjects which will have positive biopsies 180 daysafter treatment. The specificity is a measure of how well the testexcludes those without the parameter sought, in this case subjects whichwill have negative biopsies 180 days after treatment.

The next step in ROC analysis is to plot the sensitivity or truepositive rate as a function of the false positive rate or(1-specificity). The area under the curve that is created provides ameasure of the ability of the test to determine a case of disease(positive biopsy) from a case of no disease (negative biopsy). Referringto FIG. 7, the ROC curves for the two cases ((α_(site)=∞ andα_(site)=0.64 Np/cm) are shown. Curve 402 corresponds to the case ofα_(site)=∞. Curve 404 corresponds to the case of α_(site)=0.64 Np/cm.Each curve was constructed from data points, each of which correspondsto the population of Table 1 at various threshold energy density levels.An example population is given below in Table 2 wherein 2500 J/g ischosen for the energy density threshold level for the case whereinα_(site)=0.64 Np/cm. TABLE 2 Energy Density Level = 2500 J/g PositiveBiopsy Negative Biopsy Below Energy Density Level 13 2 Above EnergyDensity Level 1 3Based on the values in Table 2, the false positive rate (1-specificity)and the true positive rate (sensitivity) are 0.40 and 0.93 respectively.By changing the threshold density of the energy deposition leveladditional data points for curve 404 may be obtained to complete curve404.

The area under each curve 402, 404 is an indication of the applicabilityof the parameter being tested (density of the energy deposition) as apredictive factor. As background, for a case of random guessing, theresulting ROC curve is curve 406 which is a diagonal line from point(0,0) to (1,1) with an area under the curve of 0.5. In contrast, thearea under the curve for a ‘perfect’ test is 1.0. This test has adecision level that produces a sensitivity of 1.0 with a specificity of1.0 (i.e. no false positives and no false negatives). Turning to FIG. 7,the area under curve 402 corresponding to α_(site)=∞ is about 0.77 andthe area under curve 404 corresponding to α_(site)=0.64 Np/cm is about0.80. Based on these areas, density of the energy deposition appears tobe a strong predictor in the success or failure of a HIFU Treatment.

It should be noted that ROC analysis does not state what the decisionlevel (in this case the threshold density of the energy deposition)should be, but rather only provides a measure of the usefulness of thetest parameter, the density of the energy deposition. The thresholddensity of the energy deposition should be chosen based on balancing thecost of false positives (erroneously stating that the HIFU Treatment wasa failure) versus false negatives (erroneously stating that the HIFUTreatment was a success).

Based on the sample data analyzed, an exemplary threshold density of theenergy deposition resulting in a false negative rate of about 0 percentand a false positive rate of about 60 percent is at least about 3000 J/g(assuming infinite attenuation) and at least about 2800 J/g (assumingfinite attenuation). Another exemplary threshold density of the energydeposition resulting in a false negative rate of about 29 percent and afalse positive rate of about 40 percent is at least about 2700 J/g(assuming infinite attenuation). A further exemplary threshold densityof the energy deposition resulting in a false negative rate of about 7percent and a false positive rate of about 40 percent is at least about2500 J/g (assuming finite attenuation). Yet another exemplary thresholddensity of the energy deposition is between about 2700 J/g and about3000 J/g (assuming infinite attenuation). Still a further exemplarythreshold density of the energy deposition is between about 2500 J/g andabout 2800 J/g (assuming finite attenuation). Increasing the thresholddensity of the energy deposition results in a maximization ofsensitivity. However, setting a threshold density of the energydeposition too high could result in a rise in the risk of adverseeffects, such as rectal wall damage and/or the generation of undesirablehyperechoic features, such as non-focal hyperechoic features.

One of the benefits of using density of the energy deposition as a testfor the success or failure for HIFU Treatments is the ability toascertain the likelihood of the success of the HIFU Treatment prior toand/or during the administration of HIFU Therapy. As explained herein,the density of the energy deposition may be calculated for a proposedHIFU Treatment plan to provide the physician with a predictive indicatorof the success of such treatment plan. Further, as explained herein, thedensity of the energy deposition may be calculated for a current HIFUTreatment to advise the physician with a predictive indicator of thesuccess of such treatment plan.

The use of density of the energy deposition may be used as a guide tothe physician during the planning portion of the HIFU Treatment (Doesthe proposed plan result in a density of the energy deposition at orabove the chosen threshold density of the energy deposition?) and/orduring the actual HIFU Treatment itself (Is the treatment on pace toresult in a density of the energy deposition at or above the chosenthreshold density of the energy deposition?).

Referring to FIGS. 8A and 8B, an exemplary method of operation 600 ofHIFU System 100 is provided, wherein HIFU System 100 uses the density ofthe energy deposition as a predictive factor to determine the likelihoodof success of a given HIFU Treatment. Referring to FIG. 8A, once probe102 has been properly positioned relative to the patient, images oftissue 10 are generated and stored, as represented by block 602.Exemplary methods of imaging tissue 10 are provided herein and in thevarious patents and patent applications incorporated by referenceherein. Next, the treatment region 12 is defined, as represented byblock 604. Exemplary methods of defining treatment region 12 areprovided herein and in the various patents and patent applicationsincorporated by reference herein. As stated herein the treatment regionmay correspond to the overall prostate.

Once treatment region 12 has been defined, a treatment plan is generatedincluding a plurality of sites within treatment region 12 which will besubject to HIFU Therapy, as represented by block 606. Exemplary methodsof generating a treatment plan are provided herein and in the variouspatents and patent applications incorporated by reference herein. In oneembodiment, the treatment plan is generated based on physician input oftreatment segments to provide HIFU Therapy thereto. In this example,treatment sites are generated for each treatment segment, each treatmentsite corresponds to a location within the treatment segment which is theintersection of a transverse image and a longitudinal image.

In another embodiment, the treatment plan is generated automaticallybased on the 3-D model of tissue 10. In one example, various treatmentsegments are automatically selected each having a plurality of treatmentsites. In one variation, the treatment segments and/or treatment sitesare chosen to exclude certain tissue components from being subjected toHIFU therapy, such as the neuro-vascular bundle (NVB). As explained inU.S. Provisional Application Ser. No. 60/568,556, PCT Patent ApplicationSerial No. US2005/015648, filed May 5, 2005, designating the U.S.,titled “Method and Apparatus for the Selective Treatment of Tissue,”Attorney Docket No. FOC-P001-01, the disclosures each of which isincorporated by reference herein, the locating of the NVB isaccomplished in part through Doppler imaging of tissue 10.

In the case of automatic generation of the treatment plan, after thetreatment plan has been generated the treatment plan is analyzed todetermine the likelihood of success of the treatment plan, asrepresented by block 608. The energy expected to be deposited at eachtreatment site is summed and divided by the mass or volume of thetreatment region to obtain the density of the energy deposition. Asstated herein, the energy density may be computed for the overalltreatment region and/or for various sub-components thereof, such astreatment segments. As such, the energy density may be used as apredictive factor for the overall treatment region and/or for thevarious sub-components thereof.

By determining the likelihood of success of the automatically generatedtreatment plan, HIFU System 100 is able to make sure that theautomatically generated plan which is presented to the physician forapproval should result in a successful HIFU Treatment. It should beunderstood, that if the treatment plan or portions of the treatment plando not indicate a likelihood of success then the system automaticallyregenerates a new treatment plan which is analyzed to determine if thenew plan is likely to result in a successful HIFU Treatment. Thisprocess is repeated until a treatment plan that is likely to result insuccess is generated. In one example, HIFU System 100 attempts a limitednumber of treatment plans before it prompts the user that a successfultreatment plan cannot be generated.

It should be noted that various modifications may be made to anautomatically generated treatment plan to increase the energy densityvalue of the new automatically generated treatment plan. For example,the energy provided to one or more sites may be increased by lengtheningthe time that energy is provided (t_(ON)) and/or by increasing the totalacoustic power at the site (TAP_(site)). In another example, the numberof treatment sites is increased. In still another example, the number oftreatment sites is increased and the energy provided to one or moresites is increased.

Once a treatment plan is generated, either with physician input on thetreatment segments or automatically, (and in the case of automaticgeneration is analyzed to make sure that it is likely to result in asuccessful HIFU Treatment), the treatment plan is presented to thephysician for review, as represented by block 610. In one embodiment,the physician reviews the plan by looking at the proposed treatmentsites superimposed over various transverse and/or longitudinal images ofthe tissue 10 including the prostate. In another example, the physicianreviews the plan by looking at the proposed treatment sites superimposedover a 3-D model of the tissue 10 including the prostate and/or varioustransverse and/or longitudinal images of the tissue 10 including theprostate.

Once the physician has reviewed the treatment plan, the physician mayeither approve the treatment plan or modify the treatment plan, asrepresented by block 612. There are various reasons why the physicianmay want to modify the treatment plan. In one example, the physicianmight want to exclude treatment sites too close to certain tissuecomponents, such as the NVB, the urethra, the rectal wall, and/or theprostate capsule. In another example, the physician might want to addadditional treatment sites. In yet another example, the physician maywant to alter the total acoustic power (TAP_(site)) for varioustreatment sites or other parameters of the treatment plan. Regardless ofthe reasons, the physician has the ability to modify the treatment plan,as represented by block 614.

If the physician selected to approve the treatment plan, the treatmentplan is analyzed to determine the likelihood of success of the treatmentplan, as represented by block 616. It should be noted that if thephysician is simply approving without modification a treatment plan thathad previously been analyzed for success (block 608) then the treatmentplan does not need to be again analyzed for success at block 616.However, if the treatment plan was not automatically generated and/or ifthe physician has made modifications to the treatment plan, regardlessof whether the treatment plan had been previously analyzed, thetreatment plan is analyzed to determine the likelihood of success of thetreatment plan, as represented by block 616.

In one embodiment, to determine the likelihood of success of thetreatment plan, the energy expected to be deposited at each treatmentsite is summed and divided by the mass or volume of the treatment regionto obtain the density of the energy deposition. As stated herein, theenergy density may be computed for the overall treatment region and/orfor various sub-components thereof, such as treatment segments. As such,the energy density may be used as a predictive factor for the overalltreatment region and/or for the various sub-components thereof. Thecalculated density of the energy deposition for the overall treatmentplan or portions thereof is then compared to a reference density of theenergy deposition. In one embodiment, the planned HIFU Treatment isconsidered to likely be successful if the calculated density of theenergy deposition is equal to or exceeds the reference density of theenergy deposition. In another embodiment, the probability of success maybe computed based on the probability density functions constructed fromthe results of previous treatments. Exemplary reference density ofenergy depositions include at least about 2500 J/g, at least about 2700J/g, at least about 2800 J/g, at least about 3000 J/g, between about2500 J/g and about 2800 J/g, and between about 2700 J/g and about 3000J/g.

If the treatment plan has a likelihood of success then HIFU System 100begins the therapy portion, as represented by blocks 618 and 620. If thetreatment plan does not have a likelihood of success then HIFU System100 prompts the physician to determine if the physician wants tooverride software 109 and begin therapy, as represented by block 622.There might be several reasons why a physician would want to overridethe system and proceed with a therapy that according to the density ofthe energy deposition analysis is not likely to result in a successfultreatment. For instance, the physician might have a need to keep thetotal acoustic power low based on the structure of the tissue; thetissue might include micro-calcifications in the prostate proximate tothe rectal wall.

If the physician chooses to not override HIFU System 100, the physicianis presented with the treatment plan and permitted to modify thetreatment plan, as represented by block 614. In one embodiment, thephysician is presented with the treatment plan as it currently exists.In another embodiment, wherein the treatment plan had been modified, thephysician is presented with the treatment plan as it existed prior toany modification. In one example, the unmodified treatment plan isretrieved from memory. In another example, the unmodified treatment planis regenerated, as represented by block 606.

Referring to FIG. 8B, an exemplary therapy routine 630 is shown. Therapyroutine 630 is entered by either the approval of the treatment plan, asrepresented by block 618 in FIG. 8A, or by physician override, asrepresented by block 622 in FIG. 8A. Transducer 104 is positioned suchthat it is prepared to provide HIFU Therapy to the first treatment sitein a given treatment segment, as represented by block 632. HIFU Therapyis then provided to the selected treatment site in the selectedtreatment segment, as represented by block 634.

Images of each treatment site are taken after the respective site hasreceived HIFU Therapy. The physician monitors these images and may makechanges to the treatment plan based on these images, as represented byblock 636. For example, the physician may change the total acousticpower for subsequent treatment sites(TAP_(site d). The physician may alter the TAP) _(site) based on theimages obtained after treatment. One reason the physician may alter thetreatment is the generation of hyperechoic features after treatment.

Referring to FIGS. 9A and 9B, an illustrative treatment region 700 isshown having three treatment sites 702 a, 702 b, and 702 c. Each of thethree treatment sites 702 a-c include a focal zone 704 a-c whereatultrasound energy from transducer 104 is focused during a HIFU Therapyof the respective treatment site. In one embodiment, focal zone 704 hasa volume of about 60 mm³ and a transverse width of about 3 mm.

As is well known, the focusing of the ultrasound energy at a treatmentsite 702 results in the raising of the temperature of the tissue in andproximate to the respective treatment site 702 a, 702 b, and 702 c. Byraising the temperature enough the unwanted tissue at the respectivetreatment site 702 a, 702 b, 702 c is destroyed by ultrasound ablation.Further, it is known that at sufficient power levels that hyperechoicfeatures may be generated. (See Sanghvi et al., “Noninvasive Surgery ofProstate Tissue by High-Intensity Focused Ultrasound,” IEEE Transactionson Ultrasonics, Ferroelectrics, and Frequency Control (1996), thedisclosure of which is incorporated by reference herein.)

Referring to FIGS. 9A and 9B, four types of hyperechoic features 710,712, 714, 716 are shown. Each of FIGS. 9A and 9B generally illustrate anexemplary sector image of tissue 10. Hyperechoic feature 710 is confinedto the respective focal zone 704 of the respective treatment site 702and is therefore a focal hyperechoic feature. Further, hyperechoicfeature 710 is generally smaller than the respective focal zone 704,such as a transverse extent of the focal zone or a depth of the focalzone (viewable in a corresponding longitudinal image). Hyperechoicfeature 712 is substantially the same size as focal zone 704, such as atransverse extent of the focal zone or a depth of the focal zone, and isgenerally confined to focal zone 704. Hyperechoic feature 712 is anexemplary focal hyperechoic feature. In one example, hyperechoic feature712 a is slightly smaller than focal zone 704 a. In another example,hyperechoic feature 712 b is larger than focal zone 704 b. In apreferred example adjacent hyperechoic features, such as hyperechoicfeature 712 a, 712 b, substantially touch each other. Both hyperechoicfeature 710 and 712 are desired hyperechoic features, with hyperechoicfeature 712 being preferred.

Hyperechoic feature 714 is generally similar to hyperechoic feature 712except that hyperechoic feature 714 is migrating from the focal zone 704toward transducer 104, resulting in the treatment of tissue outside offocal zone 704. Such migration may result in the damage of tissue whichwould not otherwise be damaged, such as rectal wall 323. Hyperechoicfeature 714 is generally site specific and therefore is an exemplarynon-focal hyperechoic feature. For example, hyperechoic 714 b and 714 care each generally in line with their respective treatment sites, 704 band 704 c.

In contrast, hyperechoic feature 716 is not site specific. Hyperechoicfeature 716 corresponds to the formation of a cloud of multiple bubblesacross the tissue in the area between transducer 104 and treatmentregion 700 due to the overall heating of tissue 10. Hyperechoic feature716 blocks the HIFU energy from reaching treatment region 200 forsuccessive treatment sites 702. Examples of hyperechoic features 716 arediscussed in the paper Sanghvi et al., “Noninvasive Surgery of ProstateTissue by High-Intensity Focused Ultrasound,” IEEE Transactions onUltrasonics, Ferroelectrics, and Frequency Control (1996), thedisclosure of which is incorporated by reference herein. In oneembodiment, if hyperechoic feature 714 or hyperechoic feature 716 aredetected the HIFU Treatment should be paused and/or the TAP_(site)reduced.

The physician may reduce the TAP_(site) if hyperechoic features arevisible in the images, to prevent the formation of non-focal hyperechoicfeatures, or in order to maintain focal hyperechoic features. Thephysician may increase TAP_(site) to bring about the occurrence of focalhyperechoic features. Further, the physician may pause the HIFUTreatment due to the presence of non-focal hyperechoic features orclouds of micro bubbles. In addition, the physician may stop the HIFUTreatment.

Referring to FIG. 10, wherein HIFU System 100 is based on the Sonablate®500 HIFU System available from Focus Surgery located in Indianapolis,Ind., an exemplary partial screenshot 900 of display 111 is shown. Shownare pre-treatment images (transverse and longitudinal) 906 and 908 oftissue 10 and post-treatment images (transverse and longitudinal) 902and 904 of tissue 10. Post-treatment images 902 and 904 include arepresentation 910 of the various treatment sites 912. As seen in eachof images 902 and 904, a bright echo is observed generally confined tothe region of treatment site 912. Such bright echo is a focalhyperechoic feature 914.

Referring to FIG. 11, wherein HIFU System 100 is the Sonablate® 500 PCapparatus available from Focus Surgery located in Indianapolis, Ind., anexemplary partial screenshot 950 of display 111 is shown. Shown arepre-treatment images (transverse and longitudinal) 956 and 958 of tissue10 and post-treatment images (transverse and longitudinal) 952 and 954of tissue 10. Post-treatment images 952 and 954 include a representation960 of the various treatment sites 962. As seen in each of images 952and 954, a bright echo is observed generally in front of the region oftreatment site 962, but generally confined to the region of tissue thatenergy was applied to during the HIFU Therapy of treatment site 962.Such bright echo is a non-focal hyperechoic feature 964.

Returning to FIG. 8B, if changes are not made to the treatment plan thenit is determined if additional untreated treatment sites remain in thetreatment segment, as represented by block 638. If additional untreatedtreatment sites remain in the treatment segment, then transducer 104 ispositioned to provide HIFU Therapy to the next treatment site, asrepresented by block 640. HIFU Therapy is provided to the next treatmentsite, as represented by block 634. If additional untreated treatmentsites do not remain in the treatment segment, then a determination ismade whether there are additional untreated treatment segments in thetreatment plan, as represented by block 642. If there are additionaluntreated treatment segments, the next treatment segment is activated,as represented by block 644 and transducer 104 is positioned to providetreatment to the first treatment site of the new treatment segment asrepresented by block 632. If there is not any additional untreatedtreatment segments, the HIFU Treatment is completed and the physician isprovided with a report, as represented by block 646.

In one embodiment, the report includes a statement on whether thetreatment was likely to be successful. This is based on comparing theresulting density of the energy deposition to the set threshold value.In another embodiment, the report includes a probability of success forthe treatment. This probability is based on a library accessible bycontroller 108 containing the outcome for numerous previous treatmentand the associated density of the energy deposition.

In one embodiment, a final analysis of the treatment plan is conductedand is included in the report. The final analysis includes at least anindicator of the likelihood of success of the HIFU Treatment, such asthe density of the energy deposition of the HIFU Treatment. In oneexample, the density of the energy deposition is given for theindividual treatment segments and/or the overall treatment plan. Basedon the report, the physician may decide to return to various treatmentsegments to provide additional HIFU Therapy to one or more treatmentsites in the treatment segment, as represented by blocks 648 and 650.

Returning to block 636, if the physician decides to modify the treatmentplan during the HIFU Treatment the modified treatment plan is analyzedto determine the likelihood that it will produce a successful HIFUTreatment, as represented by block 652. In one embodiment, the modifiedtreatment plan is evaluated using the density of the energy depositiondiscussed herein. The density of the energy deposition is calculated bysumming the energy deposited at all the previously treated treatmentsites and by summing the energy to be deposited at the remainingtreatment sites of the current treatment region with the assumption thatthe current TAP level will be used for all remaining treatment sites.

In one embodiment, HIFU System 100 provides a visual cue on display 112to the physician, the visual cue providing an indication of whether thecurrent HIFU Treatment should likely be a successful HIFU Treatment. Inone example, the visual cue is a marker that is positioned along a barwith shades of red, yellow, and green that represent respectively a low,medium and high likelihood of success of the HIFU Treatment.

If the modified treatment will likely result in a successful treatment,then transducer 104 is moved to the next treatment site to be treated,as represented by blocks 654 and 638. If the modified treatment plan isnot projected to result in a successful treatment then the user mayoverride HIFU System 100, as represented by block 656. If the user doesnot override HIFU System 100, the user is again presented with theoption to modify the treatment plan, as represented by block 636. If theuser does override HIFU System 100, transducer 104 is moved to the nexttreatment site to be treated, as represented by block 638.

In one embodiment, the physician may decide to override HIFU System 100if the physician is seeing on the images subsequent to treatment, afocal hyperechoic feature and the physician wants to lower the TAP atfuture treatment sites to maintain such focal hyperechoic features. Inanother embodiment, the physician may decide to override HIFU System 100and reduce the TAP_(site) to prevent the formation of non-focalhyperechoic features or clouds of micro bubbles.

In one embodiment, HIFU System 100 monitors the images taken subsequentto treatment and makes a determination of the presence or absence ofvarious hyperechoic features. Referring to FIG. 12, an exemplary methodof operation 800 of HIFU System 100 for such monitoring is shown. HIFUSystem 100 obtains post treatment images of the treatment site justtreated with HIFU Therapy, as represented by block 802. The images areanalyzed to determine the presence of hyperechoic features, asrepresented by block 804. In one example, HIFU System 100 compares thepost treatment images to images representative of various hyperechoicfeatures stored in image library 111. In one example, image library 111contains examples of focal hyperechoic feature 710, focal hyperechoicfeature 712, non-focal hyperechoic feature 714, and clouds of microbubbles 716. Various image processing techniques, such as measuring thechange in the average image intensity in the image as a whole and/or ina portion of the image corresponding to the treatment site and/or to theregion in front of the treatment site, may be used to compare theimages.

If hyperechoic features are not present in the post treatment images,the next treatment site to be treated with HIFU Therapy is treated, asrepresented by block 806. If hyperechoic features are present in thepost treatment images, a determination is made of whether thehyperechoic features are focal hyperechoic features, the hyperechoicfeatures are non-focal hyperechoic features, or the hyperechoic featuresare clouds of micro bubbles, as represented by block 808. If thehyperechoic features are focal hyperechoic features, then the TAP_(site)for the next treatment site is either maintained or lowered slightly, asrepresented by block 810. In one example, the determination of whetherto maintain or lower the TAP_(site) is automatically made based onchanges in the image intensity or signal intensity corresponding to thetreatment region before and after application of HIFU Therapy at thetreatment site. An increase of the image intensity beyond a setthreshold for signals arriving from before the treatment region wouldindicate the need to reduce the TAP_(site), In another example, thephysician is prompted to make the determination of whether to maintainor lower the TAP_(site).

If the hyperechoic features are non-focal hyperechoic features, then thedecision is made whether the HIFU Treatment should be paused, asrepresented by block 812. In one example, this determination isautomatically made. In another example, the physician is prompted, asillustrated by block 813, to make the determination of whether to pausethe HIFU Treatment. HIFU System 100 then waits until a decision is madeto resume treatment as represented by block 814. In one example, thedecision to resume treatment is automatically made. In another example,the physician is prompted to make the determination of whether to resumethe HIFU Treatment. If the treatment is resumed or the decision was madeto not pause the treatment, then the TAP_(site) is lowered and the nexttreatment site is treated, as represented by blocks 816, 806. In oneexample, the reduction in the TAP_(site) is automatically made. Inanother example, the physician is prompted to reduce the TAP_(site).

In one embodiment, based on the detection of focal hyperechoic features,HIFU System 100 automatically lowers or maintains the TAP_(site) forsubsequent treatment sites to maintain such focal hyperechoic features.In one embodiment, based on the detection of non-focal hyperechoicfeatures, HIFU System 100 automatically lowers the TAP_(site) forsubsequent treatment sites and/or pauses the HIFU Treatment.

Referring to FIG. 16, an exemplary method 970 is provided fordetermining if a hyperechoic feature is present relative to a giventreatment site and to classify the hyperechoic feature as one of a focalhyperechoic feature or a non-focal hyperechoic feature. As representedby block 972 a post-treatment image containing the treatment site isobtained with HIFU System 100. Further, a pre-treatment image containingthe treatment site is obtained with HIFU System 100, as represented byblock 974. In one embodiment, the pre-treatment image containing thetreatment site is retrieved from image library 111 or other memoryaccessible by controller 108. Next, an image characteristic isdetermined for a given region of interest (“ROI”) for each of thepre-treatment image and the post-treatment image, as represented byblock 976. In one embodiment, the ROI generally corresponds to the sametissue location in both the pre-treatment image and the post-treatmentimage. Exemplary image characteristics include an average pixelintensity, standard deviation of pixel intensity, geometric mean of thepixel intensity, root-mean-square of the pixel intensity. In oneexample, an average pixel intensity is used for the imagecharacteristic.

Referring to FIG. 9A, exemplary ROIs 978 a, 978 b, 978 c, and 978 d areshown. ROIs 978 are illustratively shown as being generallyquadrilaterally shaped, but may be any desired shape. ROIs 978 a and 978b are generally confined to treatment site 702 a and thus generallycorrespond to the detection of focal hyperechoic features. ROIs 978 cand 978 d are generally positioned in line with transducer 104 andtreatment site 702 a and are forward of treatment site 702 a and thusgenerally correspond to the detection of non-focal hyperechoic features.Although four ROIs are shown for illustrative purposes, more or lessROIs may be implemented.

Returning to FIG. 16, for a given ROI a comparison between the imagecharacteristic for the corresponding pre-treatment ROI and thecorresponding post-treatment ROI, as represented by block 980. In theillustrated embodiment, a difference is determined between thepost-treatment average pixel intensity and the pre-treatment averagepixel intensity. This difference is compared to a threshold value storedby controller 108, as represented by block 980.

If the difference is less than the threshold value, treatment iscontinued as represented by block 982. In one embodiment, treatment iscontinued after all ROIs to be analyzed for the given treatment sitehave been analyzed by the method illustrated in FIG. 16. In one example,this includes non-focal ROIs such as 978 c and 978 d and focal ROIs suchas 978 a and 978 b. If the difference meets or exceeds the thresholdvalue then the position of the given ROI relative to the focal zone orlocation of treatment site 702 a is determined, as represented by block984. If the given ROI is positioned within the focal zone or generallywithin treatment site 702 a, treatment is continued as represented byblocks 986 and 982. If the given ROI is positioned outside of the focalzone or generally outside treatment site 702 a, the treatment is pausedand the physician is alerted, as represented by block 988.

Further, in one embodiment, a further analysis is performed prior topermitting treatment to continue. In the illustrated embodiment, afurther analysis is performed to determine if the ROI corresponds totissue that has been marked to be excluded from treatment as discussedherein, such as NVBs, or simply the location of the ROI relative to thetreatment region, such as within the focal zone, before the focal zone,within the rectal wall, and outside the prostatic capsule. If the ROIdoes not correspond to tissue marked for exclusion from treatment,treatment is permitted to continue, as represented by block 982. If thegiven ROI corresponds to tissue marked for exclusion from treatment oris positioned outside of the focal zone or generally outside treatmentsite 702 a, treatment is paused and the physician is alerted, asrepresented by block 988.

In one embodiment, HIFU System 100 is further configured to detect thepresence of acoustic obstructions in the propagation path of the HIFUenergy which are not generated as a result of the HIFU Treatment (nothyperechoic features). In the case of treating the prostate, exemplaryacoustic obstructions 820 (see FIG. 3B) include air bubbles betweenprobe 102 and rectal wall 323 or calcifications in the rectal wallitself. The presence of an acoustic obstruction blocks or at leastseverely limits the amount of HIFU energy that may proceed to theproposed treatment site during a HIFU Therapy. Similarly, the presenceof an acoustic obstruction blocks or severely limits the amount ofultrasound energy that may penetrate beyond the obstruction to image thetissue behind the obstruction. As such, the acoustic obstruction mayboth limit the imaging ability of HIFU System 100 and limit theeffectiveness of HIFU Therapy provided by HIFU System 100. Further, inthe case of HIFU Therapy tissue proximate to the obstruction may beunintentionally damaged by the application of HIFU energy, such asrectal wall 323.

One method of detecting the presence of an acoustic obstruction is toanalyze an image for one or more repetitive patterns of receivedacoustic signals. As is known, in ultrasound imaging an acoustic signalis transmitted into a medium and portions of the ultrasound signal arereflected back from portions of the medium and received by a transducer.The magnitude of these reflections are due to the properties of theportions of the medium causing the reflection. In the case of anacoustic obstruction proximate to the transducer, the acoustic signal islargely reflected by the acoustic obstruction back to the transducer. Aportion of this large reflected signal is reflected by the transducerback into the medium wherein it is again reflected by the acousticobstruction. This bouncing of the acoustic signal back-and-forth betweenthe acoustic obstruction and the transducer generates a generallyperiodic acoustic signal in time at intervals corresponding to thedistance between the transducer and the obstruction. This repetitivepattern may be used to detect the presence of the acoustic obstruction.

Referring to FIG. 13A, an exemplary method of operation 840 of HIFUSystem 100 for monitoring for acoustic obstructions is shown. HIFUSystem 100 obtains an image of the treatment site, as represented byblock 842. The image may be a two-dimensional linear image or atwo-dimensional sector image and may be a pre-treatment image or a posttreatment image. In one embodiment, the exemplary methods provided inFIGS. 13A, 13B are included in software 109 of HIFU System 100. In oneembodiment, obstruction routine 840 is automatically implemented for allimaging of the treatment region 12 including pre-treatment images andpost-treatment images.

Once the image has been obtained, a portion or sub-image is extractedfrom the image which generally corresponds to either a proposedtreatment site or a treatment site that has just been treated orattempted to be treated with HIFU energy, as represented by block 844.In one embodiment, the image and hence the sub-image correspond to anon-axis configuration between transducer 104 and the given treatmentsite. The sub-image is chosen to correspond to the lines or columns ofpixels that generally correspond to the extent of the treatment site (inthe case of a sector image generally the width of the focal zone of thetransducer at the treatment site). In one example, wherein the focalwidth is about 3 mm and there are 4 pixels/mm, twelve columns or linesare in the extracted sub-image. The intensity values of thecorresponding pixels in each line or column are averaged to produce aline image which provides the averaged intensity value as a function oftime (depth from the transducer). This line image is then analyzed todetermine if an acoustic obstruction is likely present, as representedby block 848. In one embodiment, the line image is analyzed to determineif it contains repetitive features.

An illustrative method 850 of analyzing the line image to determine ifit contains repetitive features indicating an acoustic obstruction isprovided in FIG. 13B. Method 850 is illustratively shown to detect thepresence of an acoustic obstruction proximate to a probe/tissueinterface, such as an interface between acoustic membrane 103 and rectalwall 323, during the imaging and/or the treatment of the prostatewherein probe 102 is inserted into rectum 322. An exemplary line image880 generated from an image without an acoustic obstruction is shown inFIG. 14A. An exemplary line image 890 generated from an image having anacoustic obstruction is shown in FIG. 14B. Exemplary acousticobstructions include air bubbles between probe 102 and rectal wall 323and calcification of rectal wall 323.

In one embodiment, each of images 880 and 890 are normalized tointensity values ranging from 0 to 255. Illustratively shown in FIGS.14A and 14B are upper and lower threshold lines 882A, 882B for image 880and upper and lower threshold lines 892A, 892B for image 890. In oneembodiment, the value for upper threshold 882A, 892A is set to 210 orabout 82% of the scale and the value for lower threshold 882B, 892B isset to 50 or about 20% of the scale. Further, shown in each image 880,890 are depths 884, 894 which generally correspond to the location of aninterface between acoustic membrane 103 and rectal wall 323, depths 886,896 which generally correspond to 1.5 times the location of theinterface between acoustic membrane 103 and rectal wall 323, and depths888, 898 which generally correspond to twice the location of theinterface between acoustic membrane 103 and rectal wall 323.

Referring to image 880, prior to region 884 which generally correspondsto the interface between acoustic membrane 103 and rectal wall 323, twohigh intensity features are shown. Each of these features are artificialmarkers placed on the image from which image 880 is generated and do notcorrespond to acoustic features in the treatment region.

In one embodiment, image 880 is analyzed to determine if an intensityvalue associated with depth 884 exceeds or meets a first upperthreshold, such as 882A, if an intensity value associated with depth 886is below a first lower threshold, such as 882B, and if an intensityvalue associated with depth 888 exceeds or meets a second upperthreshold. If the above three conditions are satisfied, an acousticobstruction is detected at the probe/tissue interface, such as betweenacoustic membrane 103 and rectal wall 323. If one or more of the abovethree conditions are not satisfied, an acoustic obstruction is notdetected at the probe/tissue interface, such as between acousticmembrane 103 and rectal wall 323. In one example, the second upperthreshold is not equal to the first upper threshold. In another example,the second upper threshold is equal to the first upper threshold.

Returning to FIG. 13B, each of line images 880, 890 are analyzed forpurposes of illustrating method 850. As represented in block 852, therespective line image 880, 890 is analyzed in the region proximate tothe probe/tissue interface, such as between acoustic membrane 103 andrectal wall 323, respective regions 884, 894.

In one embodiment, the probe/tissue interface (depth location along lineimage 880, 890) is determined through image processing of the linearimage 880, 890. The first step is to estimate the noise floor which isdefined as a percentage of the average signal within a portion of thelinear image 880, 890 or an image from which the respective linearimages 880, 890 is generated. In one example, the noise floor is about60% of the average intensity of the linear image 880, 890. Next, theprobe/tissue interface is defined as the location at which the pixelintensity surpasses this noise floor. In another embodiment, the user isqueried to indicate the location of the probe/tissue interface on therespective linear image 880, 890 or the image from which the respectivelinear image 880, 890 is generated. In one example, the user is promptedthrough display 112 and provides an indication of the location of theprobe/tissue interface on the image through an input with input device110.

In one embodiment, the noise floor is based on a portion or sub-image ofthe image that linear image 880, 890 is extracted from, in particularthe portion extends from the position of the transducer to half thetotal depth of the image and across the central section of the columnsof the image. In one example, the portion corresponds to about 126pixels in depth for an image which is about 6.3 cm deep at 4 pixels/mmand about ninety columns from the central section of the image withabout 45 columns on each side thereof. In another embodiment, theportion or sub-image that forms the basis of the noise level estimationmay cover other areas of the image including the whole image. Further,the portion or sub-image may include one or more non-contiguousportions, such as every Nth column from a start column to a stop column.In one example, every third column from a start column at 1 and a stopcolumn at 180. Further, the non-contiguous portions may also be indepth, such as every Mth pixel in depth from a depth of 0 mm until astopping depth. In one example, M=3 with stopping depth at maximum depthof 63 mm.

Regardless of the portions of the image used to determine the averagefor the noise level, the noise level is a percentage of this average,such as about 60% of this average. Starting at a depth position of 0 mmtest each pixel until the intensity is greater than the noise level. itshould be noted that the average intensity calculations and the test forthe probe/tissue interface excludes the artifacts added to the imagenear the transducer, as discussed herein. This position is defined asthe probe/tissue interface or in the case of treating the prostate, therectal wall position. The average rectal wall position for the linearimage is computed and is displayed for the user.

In another embodiment, the noise level is defined as discussed above,but the probe/tissue interface, the rectal wall position, is determinedfor a given treatment site as follows. The image lines (columns)pertaining to a treatment site (for example 3 mm with 4 pixels/mmresulting in 12 image lines) are extracted. The probe/tissue interfaceis found for each image line by determining the first pixel value indepth from the transducer exceeds the noise level and the averageprobe/tissue interface location based on the twelve line images is usedfor the rectal wall distance at this treatment site.

In one embodiment, the values of the pixels in respective regions 884,894 are averaged to distinguish noise from acoustic features, determinethe noise level. In one embodiment, this averaging is not triggered forthe respective image unless at least one pixel value is above therespective upper threshold 882A, 892A. Referring to FIG. 14A, the pixelsin region 884 each have an intensity value below upper threshold 882Athus indicating that a strong acoustic reflector or obstruction is notpresent in region 884. Referring to FIG. 14B, several of the pixels inregion 894 have intensity values above upper threshold 892A indicatingthat a strong acoustic reflector or obstruction is potentially presentin region 894. As such, a first check is whether the pixels inrespective region 884, 894 are above the respective upper threshold882A, 892A, as represented by block 854. In the case of image 880, theintensity values in region 884 are less than upper threshold 882A andhence treatment or imaging is continued as represented by block 856. Inthe case of image 890, the intensity values in region 894 exceed upperthreshold 892A and hence additional analysis is performed.

The next region to be analyzed is region 896 generally corresponding toabout 1.5 times the probe/tissue interface, as represented by block 858.Since the majority of the acoustic energy was reflected by an acousticobstruction proximate to rectal wall 323 a small intensity value inregion 896 should be observed because little to no acoustic energy isentering the tissue and thus reflections from deeper features beyond therectal wall 323 are indistinguishable from noise. In contrast, referringto FIG. 14A, in image 880 intensity values greater than lower threshold882B due to deeper acoustic features are observed in region 886. Assuch, a second check is to see if the intensity values in region 896 arebelow lower threshold 892B, as represented by block 860. If theintensity values exceed the lower threshold 892B then treatment orimaging is allowed to continue, as represented by block 856. In the caseof image 890 the intensity values are less than lower threshold 892B andhence additional analysis is conducted.

The next region to be analyzed is region 898 generally corresponding toabout twice the probe/tissue interface, as represented by block 862.Assuming the acoustic energy is bouncing between transducer 104 and theacoustic obstruction another bright echo (high intensity) should bepresent at region 898 if an acoustic obstruction is present. In oneembodiment, the values of the pixels in region 898 are averaged todistinguish noise from acoustic features. In one embodiment, thisaveraging is not triggered unless at least one pixel value is aboveupper threshold 892A. Referring to FIG. 14B, several of the pixels inregion 898 have intensity values above upper threshold 892A. If theintensity values did not exceed upper threshold 892A, treatment orimaging would be allowed to continue, as represented by block 856.However, the intensity values in region 898 exceed upper threshold 892Aindicating the presence of an acoustic obstruction. In response, HIFUSystem 100 pauses imaging or treatment due to the presence of anacoustic obstruction, as represented by block 866.

At this point HIFU System 100 may either simply wait a predeterminedtime followed by an attempt to re-image the portion of treatment region12, as represented by block 868 or permit system adjustment, asrepresented by block 870. Some types of acoustic obstructions, such asair bubbles introduced during the insertion of probe 102 or generated bypatient flatulence, are transient acoustic obstructions. Other types ofacoustic obstructions, such as calcification in the rectal wall 323, aregenerally permanent acoustic obstructions.

In the case of transient acoustic obstructions, the acoustic obstructionmay migrate away from the probe 102 or may be removed by moving theprobe 102 or by direct physician intervention. In the case of permanentacoustic obstructions, either the patient is not considered a goodcandidate for HIFU Treatment or the obstructed portion of treatmentregion 12 is simply not treated with HIFU Therapy. In one embodiment,wherein a phased array transducer is used, the obstructed portion oftreatment region 12 may be treated by translating the transducer oractivating a spaced apart aperture of the transducer and treating theobstructed portion from an off-axis position. An exemplary phased arraytransducer is provided in U.S. patent application Ser. No. 11/070,371,filed Mar. 2, 2005, the disclosure of which is expressly incorporated byreference herein.

Many of the methods described herein are based on or otherwise utilizethe intensity values of one or more pixels in one or more images todetect acoustic features, classify acoustic features, and/or to make oneor more treatment decisions. The intensity values of the pixels in theone or more images are based on the electrical radio frequency signalsgenerated by the transducer in response to detected acoustic energy. Assuch, in one embodiment, the herein described methods may be based onthe radio frequency signals themselves or various conditioned formsthereof instead of the intensity values of image pixels.

Although the invention has been described in detail with reference tocertain illustrated embodiments, variations and modifications existwithin the spirit and scope of the invention as described and defined inthe following claims.

1-39. (canceled)
 40. A method of treating tissue in a treatment region,the method comprising the steps of: imaging the treatment region with anultrasound transducer; automatically detecting an acoustic obstructionproximate to the ultrasound transducer; and preventing the commencementof a HIFU Treatment based upon the detection of the acoustic obstructionproximate to the ultrasound transducer.
 41. The method of claim 40,wherein the step of detecting the acoustic obstruction comprises thesteps of: analyzing a portion of an image for a repetitive pattern, anddetermining the presence of the acoustic obstruction based on thepresence of the repetitive pattern in the portion of the image.
 42. Themethod of claim 41, wherein the transducer is positioned within a probebehind an acoustic membrane of the probe and wherein the step ofanalyzing a portion of the image for a repetitive pattern comprises thesteps of: analyzing a first portion of the image at about a positioncorresponding to the acoustic membrane and the tissue to determine if afirst intensity characteristic associated with the first portion meetsor exceeds a first upper threshold; analyzing a second portion of theimage at about 1.5 times the position corresponding to the acousticmembrane and the tissue to determine if a second intensitycharacteristic associated with the second portion is below a first lowerthreshold; and analyzing a third portion of the image at about twice theposition corresponding to the acoustic membrane and the tissue todetermine if a third intensity characteristic associated with the thirdportion meets or exceeds a second upper threshold.
 43. The method ofclaim 42, wherein the position corresponding to the acoustic membranecorresponds to an interface between the tissue and the acoustic membraneof the probe.
 44. A method of treating tissue in a treatment region witha HIFU Treatment, the method comprising the steps of: initiating a HIFUTherapy to treat a portion of the tissue with an ultrasound transducer;obtaining an image of the treatment region subsequent to attempting totreat the portion of the tissue with HIFU Therapy; automaticallydetecting an acoustic obstruction proximate to the ultrasoundtransducer; and pausing the HIFU Treatment.
 45. The method of claim 44,wherein the step of detecting the acoustic obstruction comprises thesteps of: analyzing a portion of an image for a repetitive pattern, anddetermining the presence of the acoustic obstruction based on thepresence of the repetitive pattern in the portion of the image.
 46. Themethod of claim 45, wherein the transducer is positioned within a probebehind an acoustic membrane of the probe and wherein the step ofanalyzing a portion of the image for a repetitive pattern comprises thesteps of: analyzing a first portion of the image at about a positioncorresponding to the acoustic membrane and the tissue to determine if afirst intensity characteristic associated with the first portion meetsor exceeds a first upper threshold; analyzing a second portion of theimage at about 1.5 times the position corresponding to the acousticmembrane and the tissue to determine if a second intensitycharacteristic associated with the second portion is below a first lowerthreshold; and analyzing a third portion of the image at about twice theposition corresponding to the acoustic membrane and the tissue todetermine if a third intensity characteristic associated with the thirdportion meets or exceeds a second upper threshold.
 47. The method ofclaim 46, wherein the position corresponding to the acoustic membranecorresponds to an interface between the tissue and the acoustic membraneof the probe.